Natural history and life-threatening complications in Myhre syndrome and review of the literature

Eur J Pediatr. 2016 Oct;175(10):1307-15. doi: 10.1007/s00431-016-2761-3. Epub 2016 Aug 25.

Abstract

Myhre syndrome (OMIM 139210) is a rare developmental disorder inherited as an autosomal dominant trait and caused by a narrow spectrum of missense mutations in the SMAD4 gene. The condition features characteristic face, short stature, skeletal anomalies, muscle pseudohypertrophy, restricted joint mobility, stiff and thick skin, and variable intellectual disability. While most of the clinical features manifest during childhood, the diagnosis may be challenging during the first years of life. We report on the evolution of the clinical features of Myhre syndrome during childhood in a subject with molecularly confirmed diagnosis. The clinical records of 48 affected patients were retrospectively analysed to identify any early clinical signs characterizing this disorder and to better delineate its natural history. We also note that pericarditis and laryngotracheal involvement represent important life-threatening complications of Myhre syndrome that justify the recommendation for cardiological and ENT follow-up for these patients.

Conclusion: Short length/stature, short palpebral fissures, and brachydactyly with hyperconvex nails represent signs/features that might lead to the correct diagnosis in the first years of life and direct to the proper molecular analysis. We underline the clinical relevance of pericarditis and laryngotracheal stenosis as life-threatening complications of this disorder and the need for careful monitoring, in relation to their severity.

What is known: • The clinical and radiological signs of the disease in children older than 7-8 years. • Pericarditis, sometimes occurring with constrictive pericardium requiring pericardiectomy, has been reported as a recurrent feature but has not been adequately stressed in previous literature. What is New: • Short length/stature, short palpebral fissures, brachydactyly with hyperconvex nails represent clinical signs that might lead to diagnosis in the first years of life. • Review of the literature showed that pericarditis and laryngotracheal complications represent major recurrent issues in patients with Myhre syndrome.

Keywords: Cardiac tamponade; Laryngotracheal stenosis; Myhre syndrome; Pericarditis.

Publication types

  • Case Reports

MeSH terms

  • Brachydactyly
  • Child
  • Cryptorchidism / complications
  • Cryptorchidism / diagnosis*
  • Cryptorchidism / genetics
  • Facies
  • Fingers / abnormalities
  • Fingers / diagnostic imaging
  • Growth Disorders / complications
  • Growth Disorders / diagnosis*
  • Growth Disorders / genetics
  • Hand Deformities, Congenital / complications
  • Hand Deformities, Congenital / diagnosis*
  • Hand Deformities, Congenital / genetics
  • Humans
  • Intellectual Disability / complications
  • Intellectual Disability / diagnosis*
  • Intellectual Disability / genetics
  • Male
  • Mutation, Missense / genetics*
  • Nails, Malformed / physiopathology
  • Pericarditis / etiology
  • Phenotype
  • Radiography
  • Retrospective Studies
  • Smad4 Protein / genetics*

Substances

  • SMAD4 protein, human
  • Smad4 Protein

Supplementary concepts

  • Growth mental deficiency syndrome of Myhre